Tumor metastasis is the major cause of death in cancer patients. Thus, blocking tumor metastasis will significantly increase the survival rate of cancer patients and allow more moderate radiation or chemotherapy with less side-effects. One critical step of tumor metastasis is tumor cell migration and invasion. In this application, we focus on fascin, an actin-bundling protein, which is critical for tumor invasion and metastasis. Elevated expression of fascin is correlated with poor prognosis and short survival in cancer patients. In specific aim 1, we will investigate the mechanism of action of fascin inhibitors. In specific aim 2, we will further optimize fascin inhibitors. In specific aim 3, we will use animal models to examine the efficacy and toxicity of optimized fascin inhibitors.